Numerical simulation of stochastic gene circuits

Armed with increasingly fast supercomputers and greater knowledge of the molecular mechanisms of gene expression, it is now practical to numerically simulate complex networks of regulated biological reactions, or gene circuits. Using an exact stochastic simulation algorithm, we obtain an accurate time-evolution of the behavior of complex gene circuits, including the effects of fluctuations caused by highly dilute, but significant, regulatory proteins. Specifically, we examine an important gene circuit, the bistable switch, and use the stochastic simulation algorithm to develop design principles that will enable us to produce a fast and robust switch for use in future applications. We pay particular attention to different transcriptional control mechanisms and their effects on the amount of fluctuations in the system, emphasizing methods that increase certainty and improve the switching rate. (c) 2004 Elsevier Ltd. All rights reserved.